In addition to today’s exciting plenary sessions at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, several high-impact clinical trial results were reported.

KEYNOTE-407: Practice Changing (Abstract 105)

An interim analysis of the phase III KEYNOTE-407 trial showed a more than four-month longer median overall survival (OS) for metastatic squamous non–small-cell lung cancer (NSCLC) patients who received pembrolizumab plus traditional chemotherapy compared with those who received placebo plus chemotherapy.

“Squamous non–small cell lung cancer has been an orphan, almost step child, in the development of chemo[immunotherapy] for metastatic lung cancer,” said Charu Aggarwal, MD, MPH, Assistant Professor of Medicine at The Hospital of The University of Pennsylvania. “This is the first time that we are actually seeing upfront use of immunotherapy in combination with chemotherapy for squamous lung cancer.”

For KEYNOTE-407, a total of 559 participants with untreated metastatic squamous NSCLC were enrolled and randomized to receive either pembrolizumab plus chemotherapy or placebo plus chemotherapy. At the time of interim analysis, 204 participants have been randomized, 101 to the pembrolizumab plus chemotherapy arm and 103 to the placebo plus chemotherapy arm. Participants were stratified by PDL1 status.

These data suggest that pembrolizumab plus chemotherapy should become a new standard of care for the first-line treatment of metastatic squamous NSCLC across all the different levels of PDL1 expression, said study investigator, Luis Paz-Ares, MD, PhD, professor of medicine at the Hospital Universitario 12 de Octubre.

“Not only was there a PFS benefit, but there was a significant overall survival benefit with a hazard ratio of .6. There is no doubt in my mind that this benefits patients and that we need to adopt this starting today, if available,” said Dr. Aggarwal.

About the safety profile, Dr. Aggarwal said, “Overall, the toxicity profile seemed very manageable, and now we are very adept at managing immune-related toxicities since we’re been using these agents in the clinic.”

KEYNOTE-427, a single-arm, open-label design, enrolled participants with advanced clear cell or nonclear cell RCC. Eligible patients had measurable disease per RECIST criteria 1.1, no prior systemic therapy, and a Karnofsky performance status of greater than or equal to 70%. Participants received pembrolizumab at a dose of 200 mg IV every three weeks. Only data from Cohort A, which had 110 participants, were presented.

“The frequency of adverse events of special interest is consistent with what has been seen with pembrolizumab monotherapy in other tumor types,” said lead investigator David F. McDermott, MD, director of Biologic Therapy and Cutaneous Oncology Programs at Beth Israel Deaconess Medical Center.

“Treatment-related adverse events of any grade occurred in 80% of patients. Treatment-related grade 3 and 4 adverse events occurred in 30% of patients. Discontinuation due to treatment-related adverse events was reported in 11% of patients,” he said. “One patient died from treatment-related pneumonitis.”

Naomi Haas, MD, Associate Professor of Medicine at the Hospital of the University of Pennsylvania, described KEYNOTE-427 as a “really important” study.

Ipilimumab and nivolumab combination was FDA approved recently for first-line treatment in kidney cancer. “There’s a high response rate in that combination, but there’s also a lot of toxicity, and single agent pembrolizumab had an impressive response rate and less toxicity.”

She continued, “The complete response rate was not as high with the single agent pembrolizumab as it was in the ipilimumab and nivolumab combination, but it’s not clear to me that you can’t rescue some of those people later by adding a second agent and perhaps sparing people the toxicity, so I think it’s a really important first step to answering that, and I’d like to see something in the future that would include a single agent immune checkpoint inhibitor as a comparator arm in some of these combination immune checkpoint inhibitor trials.”

Erdafitinib, New Hope for Advanced Urothelial Cancer (Abstract 4503)

In the phase II study BLC2001, participants with metastatic or unresectable urothelial carcinoma who were treated with erdafitinib, an oral pan-fibroblast growth factor receptor (FGFR) inhibitor, had a 40% response rate. Three percent of patients had a complete response and 37% a partial response. These results come just a few months after the FDA granted Breakthrough Therapy Designation to erdafitinib for patients with metastatic urothelial cancer.

“This is really a very exciting trial,” commented Dr. Haas. “As in some of the other solid tumors, I think there’s a growing awareness that there are different subsets of urothelial cancer that might benefit from immune checkpoint inhibitors, and others that might benefit from other alternative treatment pathways.”

The trial enrolled advanced urothelial carcinoma patients with FGFR alterations, and 99 were treated with a median of 5 cycles of erdafitinib. Participants with prior treatment with immune check point inhibitors were eligible.

“This clinical trial with erdafitinib has met its primary objective, achieving an objective response rate of 40 percent,” said study presenter Arlene Siefker-Radtke, MD, Professor, Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center.The median PFS was 5.5 months, and the median OS at the average follow-up of 9 months was 13.8 months. Ten percent of participants discontinued treatment as a result of side effects, and 7% had serious treatment-related adverse events.

“This [trial] had a very impressive response rate in people that were pretty heavily pre-treated, and it was interesting that some of the patients who responded to this drug were resistant to immune checkpoint inhibitors,” said Dr. Haas.

The overall response rate for patients in the CORE data set (which were patients who met all study inclusion criteria) was 49% and 46% complete response at 6 months. In the trial, lisocabtagene maraleucel was evaluated at two dosing schedules (single dose vs two-dose), and across both dosing levels 93% of patients who achieved the 6-month timepoint remained in remission at last follow-up.

“This anti-CD19 CAR T-cell has remarkable efficacy in a group of highly refractory aggressive B-cell non-Hodgkin lymphoma patients,” said Caron Jacobson, MD, who discussed the study. Dr. Jacobson is Medical Director of the Immune Effector Cell Therapy Program at Dana-Farber Cancer Institute.

“The median overall survival has not been reached in this population,” noted Jeremy Abramson, MD, Clinical Director, Center for Lymphoma at Massachusetts General Hospital. Nearly 90% of patients who achieved a complete response remain alive at 1 year. “These [outcomes] are far superior of what we would have anticipated with conventional therapies in largely chemo-refractory DLBCL population.”

About toxicity, Dr. Abramson said, “I think strikingly, lisocabtagene maraleucel has shown a low and manageable toxicity profile, with very low rates of severe CRS [cytokine release syndrome] and neurotoxicity, at 1 percent and 13 percent respectively. We continue to therefore evaluate this product for an outpatient administration.”